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Recent single-cell studies of cancer in both mice and humans have identified the emergence of a myofibroblast population specifically marked by the highly restricted leucine-rich-repeat-containing protein 15 (LRRC15)1–3. However, the molecular signals that underlie the development of LRRC15+ cancer-associated fibroblasts (CAFs) and their direct impact on anti-tumour immunity are uncharacterized. Here in mouse models of pancreatic cancer, we provide in vivo genetic evidence that TGFβ receptor type 2 signalling in healthy dermatopontin+ universal fibroblasts is essential for the development of cancer-associated LRRC15+ myofibroblasts. This axis also predominantly drives fibroblast lineage diversity in human cancers. Using newly developed Lrrc15–diphtheria toxin receptor knock-in mice to selectively deplete LRRC15+ CAFs, we show that depletion of this population markedly reduces the total tumour fibroblast content. Moreover, the CAF composition is recalibrated towards universal fibroblasts. This relieves direct suppression of tumour-infiltrating CD8+ T cells to enhance their effector function and augments tumour regression in response to anti-PDL1 immune checkpoint blockade. Collectively, these findings demonstrate that TGFβ-dependent LRRC15+ CAFs dictate the tumour-fibroblast setpoint to promote tumour growth. These cells also directly suppress CD8+ T cell function and limit responsiveness to checkpoint blockade. Development of treatments that restore the homeostatic fibroblast setpoint by reducing the population of pro-disease LRRC15+ myofibroblasts may improve patient survival and response to immunotherapy.

To clarify the technical pearls of cavernous sinus molding technique with hemostatic agent injection during endoscopic endonasal pituitary surgery.All patients pretreated with cavernous sinus hemostatic agent injection molding technique for hemostasis in endoscopic endonasal surgery for pituitary adenoma resection between November 2017 and June 2021 were included. A small incision was made in the cavernous sinus wall before intracavernous manipulation. The hemostatic agent was injected with gentle pressure. It spread along the venous channels and established partial molding of the cavernous sinus. Intraoperative bleeding, surgical field score, and complications were evaluated.Thirty-eight patients with pituitary adenoma requiring cavernous sinus manipulation were pretreated with this technique. Technically, the tailored thin blunt metal tube with its 1 cm head end bended up 45° were the best instrument to accomplish injection. Multi-spot injections were preferred to control different compartments of the cavernous sinus, which both had a better effect in bleeding control and helped to reduce the influence of trigemino-cardiac reflex. Postoperative complications, including temporal lobe edema, hemorrhage, and exophthalmos were not observed.Pretreating cavernous sinus with hemostatic agent injection molding technique during endoscopic endonasal pituitary surgery is a practical, effective and safe method for intracavernous bleeding control.

Our research intended to investigate the roles of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in acute myocardial infarction (AMI) via delivery of microRNA (miR)-302d-3p. AMI mouse models were established. EVs isolated from MSCs with miR-302d-3p mimic were injected near the infarct area or co-cultured with hypoxic cardiomyocytes to evaluate their effects. The expression of NF-κB pathway-related genes and inflammatory factors was determined. AMI mice exhibited downregulated miR-302d-3p and elevated MD2 and BCL6 levels. BCL6 was negatively targeted by miR-302d-3p and could bind to MD2 promoter to upregulate MD2 expression. MSCs-EVs, MSCs-EVs carrying miR-302d-3p, or BCL6 or MD2 silencing inactivated the NF-κB pathway and alleviated infarcted area, myocardial fibrosis, inflammation, apoptosis, and cardiac dysfunction in AMI mice. Besides, MSCs-EVs, MSCs-EVs carrying miR-302d-3p, or BCL6 or MD2 silencing diminished viability and inflammation but augmented apoptosis of hypoxic cardiomyocytes. Conclusively, MSCs-EVs carrying miR-302d-3p repressed inflammation and cardiac remodeling after AMI via BCL6/MD2/NF-κB axis.

Glioma is the most common type of primary malignant tumor in the central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is a novel and distinct type of programmed cell death, playing a regulatory role in the progression of tumors. However, the role of ferroptosis or ferroptosis-related genes (FRGs) in glioma progression has not been extensively studied. In our study, a novel ferroptosis-related prognostic model, including 7 genes, was established, in which patients classified into the high-risk group had more immuno-suppressive status and worse prognosis. Among these 7 genes, we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as a possible new target for glioma treatment. Our results showed that the expression of SLC1A5 was significantly upregulated in glioblastoma tissues compared with the low-grade gliomas. In addition, SLC1A5 knockdown could significantly inhibit glioma cell proliferation and invasion, and reduce the sensitivity of ferroptosis via the GPX4-dependent pathway. Furthermore, SLC1A5 was found to be related to immune response and SLC1A5 knockdown decreased the infiltration and M2 polarization of tumor-associated macrophages. Pharmacological inhibition of SLC1A5 by V9302 was confirmed to promote the efficacy of anti-PD-1 therapy. Overall, we developed a novel prognostic model for glioma based on the seven-FRGs signature, which could apply to glioma prognostic and immune status prediction. Besides, SLC1A5 in the model could regulate the proliferation, invasion, ferroptosis and immune state in glioma, and be applied as a prognostic biomarker and potential therapeutic target for glioma.

Accumulating evidence has demonstrated the vital roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). In this study, we aimed to explore the effect of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) on ALI development. The ALI mice and cell models were constructed using lipopolysaccharide (LPS)-induced method. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, NEAT1, miR-182-5p, and WNT-inducible secreted protein 1 (WISP1) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. The level of lactate dehydrogenase (LDH) and the activity of caspase-3 were measured by specific kits. The interaction between miR-182-5p and NEAT1 or WISP1 was investigated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Protein levels were measured by Western blot assay. NEAT1 level was elevated in LPS-induced ALI mice and LPS-stimulated MH-S cells. LPS treatment repressed MH-S cell viability and promoted apoptosis and inflammation, while NEAT1 silencing restored the impacts. For mechanism analysis, NEAT1 was identified as the sponge for miR-182-5p to positively regulate WISP1 expression. Moreover, NEAT1 knockdown could accelerate cell viability and inhibit cell apoptosis and inflammation in LPS-induced MH-S cells by elevating miR-182-5p and decreasing WISP1 in LPS-exposed MH-S cells. In addition, NEAT1 deficiency blocked the activation of NF-κB pathway caused by LPS in MH-S cells. NEAT1 overexpression restrained cell viability and facilitated cell apoptosis and inflammation in LPS-exposed MH-S cells through miR-182-5p/WISP1 axis.

Background Pulmonary metastasis is the main cause of poor prognosis in osteosarcoma. Sialic acid-bound immunoglobulin lectin 15 (Siglec-15) has been demonstrated to be obviously correlated with pulmonary metastasis in osteosarcoma patients. However, the effect of Siglec-15 on autophagy in osteosarcoma remains unclear, while the role and mechanism of Siglec-15-related autophagy in lung metastasis also remain unknown. Methods The expression levels of Siglec-15 and Beclin-1 were detected in osteosarcoma tissues using immunohistochemistry (IHC). The effect of Siglec-15 on metastasis was investigated using Transwell, wound healing and animal experiments with osteosarcoma cells. Corresponding proteins were confirmed using Western blotting when Siglec-15 or Beclin-1 was silenced or overexpressed. Changes in autophagy and the cytoskeleton were detected using immunofluorescence and transmission electron microscopy. Results Siglec-15 and Beclin-1 expression was evaluated both in lung metastases and in patients who presented with pulmonary metastasis of osteosarcoma. Immunoprecipitation experiments revealed that Siglec-15 interacts directly with Beclin-1, an important autophagic protein. Moreover, loss of Siglec-15 distinctly inhibited autophagy and reduced Beclin-1/ATG14 expression. The decreased invasion and migration caused by Siglec-15 silencing could be reversed by Beclin-1 overexpression. Additionally, autophagy can promote the epithelial–mesenchymal transition (EMT) and affect cytoskeletal rearrangement, which was confirmed by overexpression or silencing of Beclin-1. Conclusions These findings confirmed the role of Siglec-15 in the regulation of autophagy and elaborated the relationship and mechanisms between autophagy and the metastasis of osteosarcoma cells.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00601-8) contains supplementary material, which is available to authorized users.

Recently, minimally invasive techniques, including endoscopic evacuation and minimally invasive catheter (MIC) evacuation, have been used for the treatment of patients with spontaneous cerebellar hemorrhage (SCH). However, credible evidence is still needed to validate the effects of these techniques. To explore the long-term outcomes of both surgical techniques in the treatment of SCH. Fifty-two patients with SCH who received endoscopic evacuation or MIC evacuation were retrospectively reviewed. Six-month mortality and the modified Rankin Scale (mRS) score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of the different surgical techniques on patient outcomes. In the present study, the mortality rate for the entire cohort was 34.6%. Univariate analysis showed that the surgical technique and preoperative Glasgow Coma Scale (GCS) score affected 6-month mortality. However, no variables were found to be correlated with 6-month mRS scores. Further multivariate analysis demonstrated that 6-month mortality in the endoscopic evacuation group was significantly lower than that in the MIC evacuation group (OR = 4.346, 95% CI 1.056 to 17.886). The 6-month mortality rate in the preoperative GCS 9–14 group was significantly lower than that in the GCS 3–8 group (OR = 7.328, 95% CI 1.723 to 31.170). Compared with MIC evacuation, endoscopic evacuation significantly decreased 6-month mortality in SCH patients. These preliminary results warrant further large, prospective, randomized studies.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury. Electronic supplementary material The online version of this article (10.1007/s12264-020-00505-7) contains supplementary material, which is available to authorized users.

Qinghai-Tibet plateau as an alpine and high-altitude area is frequently confronted with freeze-thaw stress. Recently, due to the change of global climate, the drought and salinization of soil in this area have become increasingly serious, together with low temperature, and constitute the main limiting factors for crop growth in this area. Physiological responses of blue barley to salinization (S), drought (D), and freeze-thaw (F) stress were studied. Through applying 100 mmol/L NaCl, 15% drought and freeze-thaw cycle (10, − 5, 10 °C) stress, the changes of relative water content (RWC), soluble protein, malondialdehyde (MDA), superoxide dismutase (SOD), and peroxidase (POD) in seedling leaves of 8 treatment groups (CK, S, D, DS, F, FD, FS, and FDS) were analyzed. The results showed that single stress, either NaCl, drought, or freeze-thaw, could lead to the decrease of RWC and the increase of not only the soluble protein and MDA content, but also the SOD and POD activity in leaves. During the freeze-thaw cycle, the soluble protein, MDA content, SOD, and POD activity of seedlings increased at first and gradually decreased, while RWC gradually decreased with the change of temperature. The research indicated that there were synergistic effects among the stresses of drought, NaCl, and freeze-thaw on the plant, and the compound stress could cause more serious effect on the plant compared with the single one.

BackgroundChronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH.MethodsThe second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days.DiscussionThis multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH.Trial registrationChiCTR,ChiCTR1900021659. Registered on 3 March 2019,http://www.chictr.org.cn/showproj.aspx?proj=36157.

In light of the controversies regarding the surgical treatment of adult Chiari malformation type I (CM-I) with syringomyelia, a retrospective study was conducted to evaluate the safety and efficacy of tonsillectomy followed by modified reconstruction of the cisterna magna with or without craniectomy. Between 2008 and 2017, 78 adult CM-I patients (36 males and 42 females, mean age 40.6 years old) with syringomyelia were treated with posterior fossa decompression (PFD) with tonsillectomy and modified reconstruction of the cisterna magna. Patients were divided into two study groups: group A (n = 40) underwent cranioplasty with replacement of the bone flap; group B (n = 38) underwent suboccipital craniectomy. Neurological outcomes were evaluated by traditional physician assessment (improved, unchanged, and worsened) and the Chicago Chiari Outcome Scale (CCOS). Syringomyelia outcomes were assessed radiologically. The procedure was successfully performed in all patients, and restoration of normal cerebrospinal fluid (CSF) flow was confirmed by intraoperative ultrasonography. The median postoperative follow-up was 20.3 months (range 18–60 months). Clinical improvement was evident in 66 (84.6%) patients, with no significant differences between the two groups (85.0% vs. 84.2%, P = 0.897). According to the CCOS, 36 patients (90.0%) in group A were labeled as “good” outcome, compared with that of 34 (86.8%) in group B (P = 0.734). Improvement of syringomyelia was also comparable between the groups, which was observed in 35 (87.5%) vs. 33 (86.8%) patients (P = 0.887). The postoperative overall (7.5% vs. 23.7%, P = 0.048) and CSF-related (2.5% vs. 18.4%, P = 0.027) complication rates were significantly lower in group A than group B. Tonsillectomy with modified reconstruction of the cisterna magna without craniectomy seems to be a safe and effective surgical option to treat adult CM-I patients with syringomyelia, though future well-powered prospective randomized studies are warranted to validate these findings.

Background When utilizing the retrosigmoid approach (RA), accurately identifying the transverse and sigmoid sinus transition (TSST) is a key procedure for neurosurgeons, especially in developing countries restricted by the lack of expensive devices, such as the neural navigation system and the three-dimensional volumetric image-rendered system. Before operations, a computed tomography scan is a common and cost-effective method of checking patients who suffer lesions located at the cerebellopontine angle. Therefore, we present a technique using only high-resolution computed tomography to identify the transverse and sigmoid sinus transition. Methods This retrospective study included 35 patients who underwent retrosigmoid approach operations to resect an acoustic neurinoma with the assistance of our technique. In brief, our technique contains 4 steps: (1) All patients’ 1-mm, consecutive, high-resolution computed tomographic images that clearly displayed landmarks, such as the inion, lambdoid suture, occipitomastoid suture, and the mastoid emissary foramen, were investigated initially. (2) We selected two particular slices (A and B) among all of these high-resolution computed tomographic images in which scanning planes were parallel with the line drawn from the root of the zygoma to the inion (LZI). Slice A contained both the root of the zygoma and the inion simultaneously, and slice B displayed the mastoid emissary foramen. (3) Four points (α, β, γ, δ) were arranged on slices A and B, and point α was located at the inner surface of the skull, which represents the posterior part of the sulci of the sigmoid sinus. Point β was located at the outer surface of the skull, and the line connecting them was perpendicular to the bone. Similarly, on slice B, we labeled point γ as the point that represents the posterior part of the sulci of the sigmoid sinus at the inner surface and point δ as the point located at the outer surface of the skull, and the line connecting them was also perpendicular to the bone. The distances between point β and the lambdoid suture/occipitomastoid suture and between point δ and the mastoid emissary foramen were calculated for slices A and B, respectively. (4) During the operation, a line indicating the LZI was drawn on the bone with ink when the superficial soft tissue was pushed away, and this line would cross the lambdoid suture/occipitomastoid suture. With both the crosspoint and the distance obtained from the high-resolution CT images, we could locate point β. We also used the same method to locate point δ after revealing the mastoid emissary foramen. The line connecting point β and point δ indicated the posterior border of the sigmoid sinus, and the intersection between the line and LZI indicated the inferior knee of the transverse and sigmoid sinus transition (TSST). Results All 35 patients underwent the RA craniectomies that were safely assisted by our technique, and neither the sigmoid sinus nor the transverse sinus was lacerated during the operations. Conclusion Our cost-effective technique is reliable and convenient for identifying the transverse and sigmoid sinus transition (TSST) which could be widely performed to guarantee the safety of RA craniectomy.

Endoscopic endonasal transsphenoidal resection has been accepted as a routine therapy for pituitary adenoma, but the postoperative hospital stay is typically several days long. With the advantages of reduced cost and improved patient satisfaction, the application of ambulatory surgery (AS) has developed rapidly. However, AS was still rarely adopted in neurosurgery. Here we designed an AS treatment protocol for pituitary adenoma with the endoscopic endonasal approach (EEA), and reported our initial experiences regarding the safety and efficacy of the AS protocol. 63 patients who presented with pituitary adenoma were screened at the Department of Neurosurgery, Tangdu Hospital from July to September, 2017. A total of 20 pituitary adenoma patients who met the inclusion criteria underwent EEA surgery using this evidence-based AS protocol, which emphasized adequate assessment for eligibility, full preparation to minimize invasiveness, enhanced recovery, and active perioperative patient education. Of the 20 patients enrolled, 18 were discharged on the afternoon of the operation day with a median total length of stay (LOS) of 31 hours (range, 29–32) hours. The median LOS after surgery was 6.5 (range, 5–8) hours. Two patients were transferred from the AS protocol to conventional care due to intraoperative cerebrospinal fluid leakage (one case) and an unsatisfying post-anesthetic discharge score (one case). Complications included transient and reversible mild postoperative nausea and vomiting [visual analog scale (VAS) score

Based on overlapping domain decomposition, we construct a parallel mixed finite element algorithm for solving the compressible miscible displacement problem in porous media. The algorithm is fully parallel. We consider the relation between the convergence rate and discretization parameters, including the overlapping degree of the subspaces. We give the corresponding error estimate, which tells us that only two iterations are needed to reach to given accuracy at each time level. Numerical results are presented to confirm our theoretical analysis.

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer–Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug–excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo.

Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice. We also studied possible underlying mechanisms. After PTE treatment, the neurological score and brain water content of the mice were assessed. Oxidative stress and neuronal injury were also evaluated. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity was assessed using western blot analysis. Our results indicated that PTE treatment reduces the SAH grade, neurological score, and brain water content following SAH. PTE treatment also reduced NLRP3 inflammasome activation. PTE alleviated the oxidative stress following SAH as evidenced by the dihydroethidium staining, superoxide dismutase activity, malondialdehyde content, 3-nitrotyrosie and 8-hydroxy-2-deoxyguanosine levels, and gp91phox and 4-hydroxynonenal expression levels. Additionally, PTE treatment reduced neuronal apoptosis. In conclusion, our study suggests that PTE attenuates EBI following SAH possibly via the inhibition of NLRP3 inflammasome and Nox2-related oxidative stress.

We report the design, analysis, fabrication, and measurement of a quad-band microwave metamaterial absorber that exhibits four distinct high absorption peaks at specific resonance frequencies. The proposed structure consists of a metallic hexagonal patch layer on top of a dielectric substrate with a metallic film as bottom layer. The simulation and experimental results show that the absorber presents four distinctive perfect (>90%) absorption peaks up to incidence angle of 40° for both transverse electric and transverse magnetic modes. The results prove that this kind of quad-band absorber has good performance over a wide incidence angle range and is polarization insensitive. Moreover, the experimental and numerical simulation results are essentially in agreement.

To verify whether the new Asian modified CKD-EPI equation improved the performance of original one in determining GFR in Chinese patients with CKD. A well-designed paired cohort was set up. Measured GFR (mGFR) was the result of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) dual plasma sample clearance method. The estimated GFR (eGFR) was the result of the CKD-EPI equation (eGFR1) and the new Asian modified CKD-EPI equation (eGFR2). The comparisons were performed to evaluate the superiority of the eGFR2 in bias, accuracy, precision, concordance correlation coefficient and the slope of regression equation and measure agreement. A total of 195 patients were enrolled and analyzed. The new Asian modified CKD-EPI equation improved the performance of the original one in bias and accuracy. However, nearly identical performance was observed in the respect of precision, concordance correlation coefficient, slope of eGFR against mGFR and 95 % limit of agreement. In the subgroup of GFR 60 mL min−1/1.73 m2, eGFR2 performed better than eGFR1 in terms of bias and accuracy. The new Asian modified CKD-EPI equation can lead to more accurate GFR estimation in Chinese patients with CKD in general practice, especially in the higher GFR group.

To investigate the application of the new modified Chronic Kidney Disease Epidemiology Collaboration (mCKD-EPI) equation developed by Liu for the measurement of glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and to evaluate whether this modified form is more accurate than the original one in clinical practice. GFR was determined simultaneously by 3 methods: (a) 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) dual plasma sample clearance method (mGFR), which was used as the reference standard; (b) CKD-EPI equation (eGFRckdepi); (c) modified CKD-EPI equation (eGFRmodified). Concordance correlation and Passing-Bablok regression were used to compare the validity of eGFRckdepi and eGFRmodified. Bias, precision and accuracy were compared to identify which equation showed the better performance in determining GFR. A total of 170 patients were enrolled. Both eGFRckdepi and eGFRmodified correlated well with mGFR (concordance correlation coefficient 0.90 and 0.74, respectively) and the Passing-Bablok regression equation of eGFRckdepi and eGFRmodified against mGFR was mGFR = 0.37 + 1.04 eGFRckdepi and −49.25 + 1.74 eGFRmodified, respectively. In terms of bias, precision and 30 % accuracy, eGFRmodified showed a worse performance compared to eGFRckdepi, in the whole cohort. The new modified CKD-EPI equation cannot replace the original CKD-EPI equation in determining GFR in Chinese patients with CKD.

Background Acinetobacter baumannii nosocomial ventriculitis/meningitis, especially those due to drug-resistant strains, has substantially increased over recent years. However, limited therapeutic options exist for the Acinetobacter baumannii ventriculitis/meningitis because of the poor penetration rate of most antibiotics through the blood-brain barrier. Case presentation A 57-year-old male patient developed ventriculitis from an extensively drug-resistant strain of Acinetobacter baumannii after the decompressive craniectomy for severe traumatic brain injury. The patient was successfully treated with intraventricular and intravenous polymyxin B together with intravenous tigecycline. Conclusions The case illustrates intraventricular polymyxin B can be a therapeutic option against extensively drug-resistant Acinetobacter baumannii ventriculitis.

Tandem catalytic systems, consisting of ethylene bis(indenyl) zirconium dichloride with two different cocatalysts, alkylaluminum (diethylaluminium chloride or trialkylaluminum) and methylaluminoxane, were employed in preparing branched polyethylene from ethylene as sole monomer. The catalytic system rac-Et(Ind)2ZrCl2/AlEt2Cl/MAO exhibited high incorporation (29.0/1000C). The oligomerization and copolymerization reaction conditions in the tandem catalytic system, as well as the different cocatalysts, have effects on the catalytic activity and the properties of the obtained polymer, such as melting temperature, crystallinity, molecular weight and molecular weight distribution. Moreover, the oligomerization reaction condition is the main factor in altering the properties and structures of polyethylene.

Objective To observe the efficacy of warm needling in canicular days in treating knee osteoarthritis (KOA).

Background Growing evidence suggests that hepatitis C virus (HCV) contributes to hepatocellular carcinoma (HCC) by directly modulating oncogenic signaling pathways. Protein phosphatase magnesium-dependent 1A (PPM1A) has recently emerged as an important tumor suppressor as it can block a range of tumor-centric signaling pathways through protein dephosphorylation. However, the role and regulatory mechanisms of PPM1A in HCV-infected cells have not been reported. Methods Total, cytoplasmic, and nuclear PPM1A protein after HCV infection or overexpression of HCV nonstructural protein 3 (NS3) were detected by western blotting. The expression of PPM1A in normal liver and HCV-related HCC tissues was quantified by immunohistochemistry. The effects of HCV infection and NS3 expression on the PPM1A protein level were systematically analyzed, and the ubiquitination level of PPM1A was determined by precipitation with anti-PPM1A and immunoblotting with either anti-ubiquitin or anti-PPM1A antibody. Finally, the roles of NS3 and PPM1A in hepatoma cell migration and invasion were assessed by wound healing and transwell assays, respectively. Results HCV infection and replication decreased PPM1A abundance, mediated by NS3, in hepatoma cells. Compared to normal liver tissues, the expression of PPM1A was significantly decreased in the HCC tumor tissues and adjacent non-tumor tissues. NS3 directly interacted with PPM1A to promote PPM1A ubiquitination and degradation, which was dependent on its protease domain. Blockade of PPM1A through small interfering RNA significantly promoted HCC cell migration, invasion, and epithelial mesenchymal transition (EMT), which were further intensified by TGF-β1 stimulation, in vitro. Furthermore, restoration of PPM1A abrogated the NS3-mediated promotion of HCC migration and invasion to a great extent, which was dependent on its protein phosphatase function. Conclusions Our findings demonstrate that the HCV protein NS3 can downregulate PPM1A by promoting its ubiquitination and proteasomal degradation, which might contribute to the migration and invasion of hepatoma cells and may represent a new strategy of HCV in carcinogenesis. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0510-8) contains supplementary material, which is available to authorized users.

Hyperbaric oxygen (HBO) therapy and memantine, a non-competitive NMDA antagonist, are both promising treatment strategies for improving stroke prognosis. However, HBO’s narrow therapeutic time window (

Objective To observe the clinical effect of tuina reduction manipulation on leg length discrepancy and lumbosacral pain due to sacroiliac joint subluxation.

A new full time-domain nonlinear coupled method has been established and then applied to predict the responses of a Truss Spar in irregular wave. For the coupled analysis, a second-order time-domain approach is developed to calculate the wave forces, and a finite element model based on rod theory is established in three dimensions in a global coordinate system. In numerical implementation, the higher-order boundary element method (HOBEM) is employed to solve the velocity potential, and the 4th-order Adams-Bashforth-Moultn scheme is used to update the second-order wave surface. In deriving convergent solutions, the hull displacements and mooring tensions are kept consistent at the fairlead and the motion equations of platform and mooring-lines/risers are solved simultaneously using Newmark-β integration scheme including Newton-Raphson iteration. Both the coupled quasi-static analysis and the coupled dynamic analysis are performed. The numerical simulation results are also compared with the model test results, and they coincide very well as a whole. The slow-drift responses can be clearly observed in the time histories of displacements and mooring tensions. Some important characteristics of the coupled responses are concluded.

Phosphorylation of the NOD-like receptor NLRC4 is essential for activation of the NLRC4 inflammasome complex in response to bacterial stimuli. The NOD-like receptor NLRC4 acts as an inflammasome receptor and is an important part of the innate immune system. Vishva Dixit and colleagues now show that NLRC4 phosphorylation is essential for activation of the NLRC4 inflammasome complex in response to bacterial stimuli. Biochemical purification of the NLRC4-phosphorylating activity and a screen of kinase inhibitors suggest that PKCδ is the NLRC4 kinase involved. NLRC4 is a cytosolic member of the NOD-like receptor family that is expressed in innate immune cells. It senses indirectly bacterial flagellin and type III secretion systems, and responds by assembling an inflammasome complex that promotes caspase-1 activation and pyroptosis1,2,3,4,5,6. Here we use knock-in mice expressing NLRC4 with a carboxy-terminal 3×Flag tag to identify phosphorylation of NLRC4 on a single, evolutionarily conserved residue, Ser 533, following infection of macrophages with Salmonella enterica serovar Typhimurium (also known as Salmonella typhimurium). Western blotting with a NLRC4 phospho-Ser 533 antibody confirmed that this post-translational modification occurs only in the presence of stimuli known to engage NLRC4 and not the related protein NLRP3 or AIM2. Nlrc4−/− macrophages reconstituted with NLRC4 mutant S533A, unlike those reconstituted with wild-type NLRC4, did not activate caspase-1 and pyroptosis in response to S. typhimurium, indicating that S533 phosphorylation is critical for NLRC4 inflammasome function. Conversely, phosphomimetic NLRC4 S533D caused rapid macrophage pyroptosis without infection. Biochemical purification of the NLRC4-phosphorylating activity and a screen of kinase inhibitors identified PRKCD (PKCδ) as a candidate NLRC4 kinase. Recombinant PKCδ phosphorylated NLRC4 S533 in vitro, immunodepletion of PKCδ from macrophage lysates blocked NLRC4 S533 phosphorylation in vitro, and Prkcd−/− macrophages exhibited greatly attenuated caspase-1 activation and IL-1β secretion specifically in response to S. typhimurium. Phosphorylation-defective NLRC4 S533A failed to recruit procaspase-1 and did not assemble inflammasome specks7 during S. typhimurium infection, so phosphorylation of NLRC4 S533 probably drives conformational changes necessary for NLRC4 inflammasome activity and host innate immunity.

Although Homer 1, of the postsynaptic density, regulates apoptosis, the signaling mechanisms are not fully elucidated. In this study, we found that tumor necrosis factor-α (TNF-α)/cycloheximide (CHX) treatment transiently increased Homer 1a (the short variant of Homer 1), but did not affect Homer 1b/c (the long variant of Homer 1). Overexpression of Homer 1a blocked TNF-α/CHX-induced apoptotic cell death, whereas inhibition of Homer 1a induction enhanced the pro-apoptotic effect of TNF-α/CHX treatment. Moreover, brain-derived neurotrophic factor, as a potential activator of endogenous Homer 1a, inhibited apoptotic cell death after TNF-α/CHX treatment through induction of Homer 1a. Since three major mitogen-activated protein kinase (MAPK) pathways have important roles in apoptosis, we examined if Homer 1a is involved in the effects of MAPK pathways on apoptosis. It was shown that inhibition of the ERK1/2 pathway increased the expression and the protective effect of Homer 1a, but inhibition of the p38 pathway produced the opposite effect. Cross-talk among MAPK pathways was also associated with the regulation of Homer 1a during apoptotic cell death. Blocking the p38 pathway increased the activity in the ERK1/2 pathway, while inhibition of ERK1/2 pathway abolished the effect of p38 inhibitor on Homer 1a. Furthermore, Homer 1a reversely affected the activation of MAPK pathways. These findings suggest that Homer 1a plays an important role in the prevention of apoptotic cell death and contributes to distinct regulatory effects of MAPK pathways on apoptotic cell death.

Several previous studies utilizing selective pharmacological antagonists have demonstrated that type 5 metabotropic glutamate receptors (mGluR5) are potential therapeutic targets for the treatment of numerous disorders of the central nervous system, but the role of mGluR5 activation in traumatic brain injury (TBI) is not fully understood. Here in an in vitro TBI model, the mGluR5 agonist (RS)-2-chloro-5- hydroxyphenylglycine (CHPG) and the positive allosteric modulators 3-cyano-N-(1,3- diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) were used to investigate the neuroprotective potency of mGluR5 activation. Data showed that CHPG and CDPPB suppressed the increase of LDH release and caspase-3 activation induced by traumatic neuronal injury in a dose-dependent manner, and the salutary effects were also present when these compounds were added 1 h after injury. Western blot was used to examine the activation of three members of mitogen-activated protein kinases: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). CHPG and CDPPB enhanced the activation of ERK after traumatic neuronal injury, and PD98059 and U0126, two selective MEK/ERK inhibitors, partly revised the protective effects. Furthermore, we also investigated the role of protein kinase C (PKC) in CHPG and CDPPB-induced neuroprotection. With the pretreatment of chelerythrine chloride, a PKC inhibitor, the surpressing effects of CHPG and CDPPB on traumatic injury-evoked LDH release and caspase-3 activation were blocked. All of these findings extended the protective role of mGluR5 activation in an in vitro model of TBI and suggested that these protective effects might be mediated by the PKC-dependent activation of MEK/ERK pathway. These results may have important implications for the development of mGluR5 modulators to treat TBI.

Herein, we present an adult case of medulloblastoma who received chemotherapy, radiation therapy and stem cell transplantation, and underwent multiple surgical resections for what were thought to be recurrences; however pathology confirmed a diagnosis of relapsing tumefactive lesions. This phenomenon seems to be a consequence of stem cell transplantation rather than a simple radiation treatment effect.

Let f be a Maass eigenform that is a new form of level N on Γ0(N), with Laplace eigenvalue 1/4 + νf2. Then, all its Fourier coefficients {λf(n)}n=1∞ are real, and we may normalize so that λf(1) = 1. It is proved, in this paper, that the first sign change in the sequence {λf(n)}n=1∞ occurs at some n satisfying n ≪ {(3+|νf|2)N}1/2−δ and (n, N) = 1. This generalizes the previous results for holomorphic Hecke eigenforms.

Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell–cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

To compare the short-term effect of treatment with atorvastatin and rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia.Sixty-nine patients with hypercholesterolemia were randomly assigned to receive 10 mg/day of atorvastatin or rosuvastatin for 12 weeks. Inflammatory biomarkers, including highsensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-9 (MMP-9), and endothelin (ET-1), plasminogen activator inhibitor type 1 (PAI-1) and plasma tissue plasminogen activator (tPA), adiponectin, and lipid profiles were measured before and after statin therapy.Atorvastatin and rosuvastatin both lowered levels of hs-CRP, MMP-9, PAI-1, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) from baseline values, with rosuvastatin lowering TC and LDL-C to a greater extent than atorvastatin (P0.05). Adiponectin level increase was 15% higher than that at baseline with atorvastatin (P0.05) but 67% higher with rosuvastatin (P0.05).Therapy with both statins not only significantly improved lipid profiles but also decreased levels of vascular biomarkers hs-CRP, MMP-9, and PAI-1; however, only rosuvastatin increased serum adiponectin levels significantly in patients with hypercholesterolemia, which could imply a beneficial effect in coronary artery disease.

This paper presents a microfluidic chip for highly efficient separation of red blood cells (RBCs) from whole blood on the basis of their native magnetic properties. The glass chip was fabricated by photolithography and thermal bonding. It consisted of one inlet and three outlets, and a nickel wire of 69-microm diameter was positioned in the center of a separation channel with 149-microm top width and 73-microm depth by two parallel ridges (about 10 microm high). The two ridges were formed simultaneously during the wet etching of the channels. The nickel wire for generating the magnetic gradient inside the separation channel was introduced from the side of the chip through a guide channel. The external magnetic field was applied by a permanent magnet of 0.3 T placed by the side of the chip and parallel to the main separation channel. The RBCs were separated continuously from the 1:40 (v/v) diluted blood sample at a flow rate in the range 0.12-0.92 microL/min (9-74 mm/min) with the chip, and up to 93.7% of the RBCs were collected in the middle outlet under a flow rate of 0.23 microL/min. The cell sedimentation was alleviated by adjusting the specific density of the supporting media with bovine serum albumin. Quantum dot labeling was introduced for visual fluorescence tracking of the separation process. The uneven distribution phenomenon of the blood cells around the nickel wire was reported and discussed.

Background China has the second highest caseload of multidrug-resistant tuberculosis (MDR-TB) in the world. In 2009, the Chinese government agreed to draw up a plan for MDR-TB prevention and control in the context of a comprehensive health system reform launched in the same year. Discussion China is facing high prevalence rates of drug-resistant TB and MDR-TB. MDR-TB disproportionally affects the poor rural population and the highest rates are in less developed regions largely due to interrupted and/or inappropriate TB treatment. Most households with an affected member suffer a heavy financial burden because of a combination of treatment and other related costs. The influential Global Fund programme for MDR-TB control in China provides technical and financial support for MDR-TB diagnosis and treatment. However, this programme has a fixed timeline and cannot provide a long term solution. In 2009, the Bill and Melinda Gates Foundation, in cooperation with the National Health and Family Planning Commission of China, started to develop innovative approaches to TB/MDR-TB management and case-based payment mechanisms for treatment, alongside increased health insurance benefits for patients, in order to contain medical costs and reduce financial barriers to treatment. Although these efforts appear to be in the right direction, they may not be sufficient unless (a) domestic sources are mobilized to raise funding for TB/MDR-TB prevention and control and (b) appropriate incentives are given to both health facilities and their care providers. Summary Along with the on-going Chinese health system reform, sustained government financing and social health protection schemes will be critical to ensure universal access to appropriate TB treatment in order to reduce risk of developing MDR-TB and systematic MDR-TB treatment and management. Electronic supplementary material The online version of this article (doi:10.1186/s40249-016-0103-3) contains supplementary material, which is available to authorized users.

In this paper, direct whole blood PCR amplifications on a static chip thermostat without sample purifications are demonstrated; in these amplifications, problems such as cross-interferences and contaminations could be avoided. The amplification conditions, such as the compositions of reagents and thermal programs, were investigated systematically by a GeneAmp PCR system with a native p53 gene segment (about 543 bp) of human genome and an exterior lambda DNA segment (about 500 bp) as targets. Direct amplifications of p53 and K-ras (about 157 bp) gene segments from 0.5 microL blood samples were successfully demonstrated by a static PCR chip with an indium tin oxide glass substrate. The chip thermostat has a typical size of 25 mm x 25 mm, and a polyethylene tube was used as the PCR vial on the glass surface of the chip. Fuzzy proportional integration-differentiation algorithms were adopted in temperature controls of the chip with an aid of a micro-Pt100 sensor. In the direct PCR with the thermostat chip, the whole process only involves automatic thermal programs. This work demonstrated that a chip PCR for field test without desktop facilities is possible either for a point of care test or for forensic analysis.

Genetically modified mouse strains derived from embryonic stem (ES) cells are powerful tools for gene function analysis. ES cells from the C57BL/6 mouse strain are not widely used to generate mouse models despite the advantage of a defined genetic background. We assessed genetic variation in six such ES cell lines with 275 SSLP markers. Compared to C57BL/6, Bruce4 differed at 34 SSLP markers and had significant heterozygosity on three chromosomes. BL/6#3 and Dale1 ES cell lines differed at only 3 SSLP makers. The C2 and WB6d ES cell lines differed at 6 SSLP markers. It is important to compare the efficiency of producing mouse models with available C57BL/6 ES cells relative to standard 129 mouse strain ES cells. We assessed genetic stability (the tendency of cells to become aneuploid) in 110 gene-targeted ES cell clones from the most widely used C57BL/6 ES cell line, Bruce4, and 710 targeted 129 ES cell clones. Bruce4 clones were more likely to be aneuploid and unsuitable for ES cell-mouse chimera production. Despite their tendency to aneuploidy and consequent inefficiency, use of Bruce4 ES cells can be valuable for models requiring behavioral studies and other mouse models that benefit from a defined C57BL/6 background.

Strain rate (SR) provides a quantitative segmental analysis of myocardial function. However, the use of SR with stress echocardiography to determine the ischemic myocardium has not been completely investigated. The present study aimed to determine the changes in systolic function of the ischemic myocardium by strain-rate imaging (SRI) with adenosine stress echocardiography.Stenosis and complete occlusion of coronary arteries were produced in 11 canine models by constricting the left anterior descending coronary artery (LAD). Myocardial longitudinal strain with adenosine was measured at baseline and during ischemia and infarction.Strain and SR did not differ during ischemia and infarction as compared with that at baseline in non-LAD segments or after adenosine treatment. As compared with baseline, during ischemia, LAD segments showed significantly decreased peak systolic SR (SR(peak sys)) (P0.05) and significantly increased ratio of postsystolic strain (epsilon(ps)) to strain during ejection time (epsilon(et)) (epsilon(ps)/epsilon(et)) (P0.05); epsilon(max) and epsilon(et) were reduced slightly, epsilon(ps) and the ratio of epsilon(ps) to maximal systolic strain (epsilon(max))(epsilon(ps)/epsilon(max)) were increased minimally, but had no significance(P0.05). During infarction, the epsilon(ps) and the ratios of epsilon(ps)/epsilon(max) and epsilon(ps)/epsilon(et) were increased markedly (P0.01) and epsilon(et) and SR(peak sys) decreased as compared with that at baseline and during ischemia, whereas epsilon(max) was reduced only with at baseline (P0.01). After adenosine treatment, in the non-LAD segments, the values of strain and SR did not change at baseline or during ischemia and infarction and in LAD segments, values did not change at baseline and during infarction. However, during ischemia, SR(peak sys) and epsilon(et) were significantly reduced (P0.05), whereas epsilon(ps), epsilon(ps)/epsilon(max) and epsilon(ps)/epsilon(et) were increased (P0.05 and0.01, respectively).Combined with adenosine stress echocardiography, SRI can quantitatively differentiate the ischemic from non-ischemic myocardium. epsilon(ps)/epsilon(max) and epsilon(ps)/epsilon(et) can be used as objective indices to identify the ischemic myocardium.

As is well established, mastery to precise control of the layer number, stacking order of graphene, and the size of single-crystal monolayer graphene is very important for both fundamental interest and practical applications. In this report, millimeter-sized single-crystal monolayer graphene has been synthesized to multilayer graphene on Cu by chemical vapor deposition. The relationship of the growth process between monolayer graphene and multilayer graphene is investigated carefully. Besides the general multilayer graphene with Bernal stacking order, parts of multilayer graphene with non-Bernal stacking order were modulated under optimized growth conditions. The oxide nanoparticle on the Cu surface derived from annealing has been found to play the key role in nucleation. In addition, the hydrogen concentration impacts significantly on the layer number and shape of the graphene. Moreover, a possible mechanism was proposed to understand the growth process discussed above, which may provide an instruction to graphene growth on Cu by chemical vapor deposition. Electronic supplementary material The online version of this article (doi:10.1186/s11671-015-1164-0) contains supplementary material, which is available to authorized users.

Hegang Ren, Min Yang, Yujin Liu, Binyuan Liu*, Jiayan Qu, Yanji Wang, and Il Kim* Institute of Polymer Science and Engineering, Hebei University of Technology, Tianjin 300130, P. R. China Institute of Green Chemical Technology, School of Chemical Engineering&Technology, Hebei University of Technology, Tianjin 300130, P. R. China The WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Busan 609-735, Korea

In this paper, we present a constraint-based model of cooperative agents for information systems dialogues, with an emphasis on how the agents detect and resolve situations in which the user's information needs have been over-constrained. The constraint-based model of the information agents integrates and extends the AI techniques of constraint satisfaction, solution synthesis and constraint hierarchy, providing an incremental computational mechanism for constructing and maintaining partial parallel solutions. Such a mechanism supports immediate detection of over-constrained situations. In addition, we explore using the knowledge in the solution synthesis network to support different relaxation strategies to support cooperative dialogue behaviors.

The paper first introduces the concepts, method and recent development of WebGIS technology, then discusses the functionality and application prospect of WebGIS in the field of seismological study, finally the paper gives a presentation on application of WebGIS to seismological study and constructs a WebGIS information system for seismological study by using GIS component MO/MOIMS. The system based on Browser/Server architecture can implements the sharing of spatial data and GIS applications and partly collaborating work. This WebGIS solution has important significance for seismological study and deserves to further research.

Oxidative/nitrative stress plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Notch1 participates in the regulation of cardiogenesis and cardiac response to hypertrophic stress, but the function of Notch1 signaling in MI/R has not been explored. This study aims to determine the role of Notch1 in MI/R, and investigate whether Notch1 confers cardioprotection. Notch1 specific small interfering RNA (siRNA, 20 μg) or Jagged1 (a Notch ligand, 12 μg) was delivered through intramyocardial injection. 48 h after injection, mice were subjected to 30 min of myocardial ischemia followed by 3 h (for cell apoptosis and oxidative/nitrative stress), 24 h (for infarct size and cardiac function), or 2 weeks (for cardiac fibrosis and function) of reperfusion. Cardiac-specific Notch1 knockdown resulted in significantly aggravated I/R injury, as evidenced by enlarged infarct size, depressed cardiac function, increased myocardial apoptosis and cardiac fibrosis. Downregulation of Notch1 increased expression of inducible NO synthase (iNOS) and gp(91phox), enhanced the production of NO metabolites and superoxide, as well as their cytotoxic reaction product peroxynitrite. Moreover, Notch1 blockade also reduced phosphorylation of endothelial NO synthase (eNOS) and Akt, and increased expression of PTEN, a key phosphatase involved in the regulation of Akt phosphorylation. In addition, activation of Notch1 by Jagged1 or administration of peroxynitrite scavenger reduced production of peroxynitrite and attenuated MI/R injury. These data indicate that Notch1 signaling protects against MI/R injury partly though PTEN/Akt mediated anti-oxidative and anti-nitrative effects.

ZnO nanorod arrays (NRAs) on transparent conductive oxide (TCO) films have been grown by a solution-free, catalyst-free, vapor-phase synthesis method at 600°C. TCO films, Al-doped ZnO films, were deposited on quartz substrates by magnetron sputtering. In order to study the effect of the growth duration on the morphological and optical properties of NRAs, the growth duration was changed from 3 to 12 min. The results show that the electrical performance of the TCO films does not degrade after the growth of NRAs and the nanorods are highly crystalline. As the growth duration increases from 3 to 8 min, the diffuse transmittance of the samples decreases, while the total transmittance and UV emission enhance. Two possible nanorod self-attraction models were proposed to interpret the phenomena in the sample with 9-min growth duration. The sample with 8-min growth duration has the highest total transmittance of 87.0%, proper density about 75 μm−2, diameter about 26 nm, and length about 500 nm, indicating that it can be used in hybrid solar cells.

Impaired mitochondrial biogenesis causes skeletal muscle damage in diabetes. However, whether and how mitochondrial biogenesis is impaired in the diabetic heart remains largely unknown. Whether adiponectin (APN), a potent cardioprotective molecule, regulates cardiac mitochondrial function has also not been previously investigated. In this study, electron microscopy revealed significant mitochondrial disorders in ob/ob cardiomyocytes, including mitochondrial swelling and cristae disorientation and breakage. Moreover, mitochondrial biogenesis of ob/ob cardiomyocytes is significantly impaired, as evidenced by reduced Ppargc-1a/Nrf-1/Tfam mRNA levels, mitochondrial DNA content, ATP content, citrate synthase activity, complexes I/III/V activity, AMPK phosphorylation, and increased PGC-1α acetylation. Since APN is an upstream activator of AMPK and APN plasma levels are significantly reduced in ob/ob mice, we further tested the hypothesis that reduced APN in ob/ob mice is causatively related to mitochondrial biogenesis impairment. One week of APN treatment of ob/ob mice activated AMPK, reduced PGC-1α acetylation, increased mitochondrial biogenesis, and attenuated mitochondrial disorders. In contrast, knocking out APN inhibited AMPK-PGC-1α signaling and impaired both mitochondrial biogenesis and function. The ob/ob mice exhibited lower survival rates and exacerbated myocardial injury after MI, when compared to controls. APN supplementation improved mitochondrial biogenesis and attenuated MI injury, an effect that was almost completely abrogated by the AMPK inhibitor compound C. In high glucose/high fat treated neonatal rat ventricular myocytes, siRNA-mediated knockdown of PGC-1α blocked gAd-enhanced mitochondrial biogenesis and function and attenuated protection against hypoxia/reoxygenation injury. In conclusion, hypoadiponectinemia impaired AMPK-PGC-1α signaling, resulting in dysfunctional mitochondrial biogenesis that constitutes a novel mechanism for rendering diabetic hearts more vulnerable to enhanced MI injury.